An acyliminium route to a combined isoindoline-indolizidine scaffold

The chemical merging of isoindoline and indolizidine structural frameworks may qualify as an entry into a unique set of pseudo-natural products with therapeutic potential. Benzylic acyliminium ions derived from isoindolinones have proven to be effective in generating polycyclic structures which are of interest in both the natural products and synthetic medicinal arenas. In this work, the utilization of an intramolecular acyliminium ion reaction in conjunction with a substrate bearing a suitably-disposed unsaturated cyclic appendage gives rise to a tetracyclic carbon framework which is hitherto unknown in the natural product realm. The overall process has the potential to accommodate substituents at several positions of the tetracycle once formed. The conditions for the generation of the tetracyclic framework and the routes and reactions for the preparation of its functional derivatives such as ester, hydroxyl, mesylate, azide, and amine are detailed.